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| EM-3 Targets Stat3 to Induce Apoptosis, G2/M Cell Cycle Arrest and Reduce the Proportion of SP Cells in Nasopharyngeal Carcinoma |
| LI Zhen-hua1, LI Cui-ping2, ZHANG Xiang-qiang1, DAI Li-ting1, TANG Meng-si4, WANG Guo-cai3, JIANG Jian-wei1, CAO Ming-rong1 |
1. Department of Biochemistry, Medical College, Jinan University, Guangzhou 510632, China;
2. Feicheng Environment Protection Agency, Taian 271600, China;
3. Institute of Traditional Chinese Medicine and Nature Products, College of Pharmacy, Guangzhou 510630, China;
4. Cancer Center of Sun Yat-sen University, Guangzhou 510060, China |
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Abstract Objective: To investigate the antitumor mechanism of EM-3, a ethanol extracts from Elephantopus mollis H.B.K, in nasopharyngeal carcinoma. Methods: The effects of EM-3 on the cell proliferative and migratory activity of CNE2, CNE2-S18 and L02 cells were detected by MTT assay, colony formation assay and cell scratch assay. Cell apoptosis was evaluated by Annexin V-FITC/PI double staining. Cell cycle was evaluated by PI single staining. The percentage of SP cells from CNE2-S18 cells was analyzed by fluorescence-activated cell sorting (FACS) assay. Expressions of apoptosis-relative proteins, cycle-relative, migration-relative proteins and cancer stem cells related proteins in CNE2 cells were measured by Western blotting. Result: The proliferation and migration of nasopharyngeal carcinoma was inhibited by EM-3 in a dose and time-dependent manner. Colony formation assays showed that EM-3 decreased colony formation compared with control. Flow cytometry analysis showed an increase of the percentage of apoptotic cells and G2/M phase in a dose-dependent manner treated with EM-3. FACS assays demonstrated that EM-3 decreased the percentage of CNE2-S18 stem-like SP cells. EM-3 downregulated the expression of xIAP, Bcl-2, Cyclin D1, MMP2(high drug concentration), MMP9, p-Met, Oct4(high drug concentration) and Sox2 with different concentrations. In addition, active bands of Caspase-9, Caspase-3 and PARP could be detected using Western blotting. But the expression of Cyclin B1 and Bax was upregulated. Conclusions: EM-3 induces the apoptosis and G2/M cycle arrest by down-regulation of Stat3 signaling pathway. In addition, EM-3 inhibits cell migration by MMPS pathway and can effectively reduce the maintenance of CNE2-S18 stem-like SP cells.
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Received: 28 September 2015
Published: 19 November 2015
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Cite this article:
LI Zhen-hua, LI Cui-ping, ZHANG Xiang-qiang, DAI Li-ting, TANG Meng-si, WANG Guo-cai, JIANG Jian-wei, CAO Ming-rong. EM-3 Targets Stat3 to Induce Apoptosis, G2/M Cell Cycle Arrest and Reduce the Proportion of SP Cells in Nasopharyngeal Carcinoma. China Biotechnology, 2016, 36(3): 1-10.
URL:
https://manu60.magtech.com.cn/biotech/DOI:10.13523/j.cb.20160301 OR https://manu60.magtech.com.cn/biotech/Y2016/V36/I3/1
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